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Background: Multiparametric magnetic resonance imaging (mpMRI) for prostate cancer detection without careful patient selection may lead to excessive resource utilization and costs., Objective: To develop and validate a clinical tool for predicting the presence of high-risk lesions on mpMRI., Design, Setting, and Participants: Four tertiary care centers were included in this retrospective and prospective study (BiRCH Study Collaborative). Statistical models were generated using 1269 biopsy-naive, prior negative biopsy, and active surveillance patients who underwent mpMRI. Using age, prostate-specific antigen, and prostate volume, a support vector machine model was developed for predicting the probability of harboring Prostate Imaging Reporting and Data System 4 or 5 lesions. The accuracy of future predictions was then prospectively assessed in 214 consecutive patients., Outcome Measurements and Statistical Analysis: Receiver operating characteristic, calibration, and decision curves were generated to assess model performance., Results and Limitations: For biopsy-naïve and prior negative biopsy patients (n=811), the area under the curve (AUC) was 0.730 on internal validation. Excellent calibration and high net clinical benefit were observed. On prospective external validation at two separate institutions (n=88 and n=126), the machine learning model discriminated with AUCs of 0.740 and 0.744, respectively. The final model was developed on the Microsoft Azure Machine Learning platform (birch.azurewebsites.net). This model requires a prostate volume measurement as input., Conclusions: In patients who are naïve to biopsy or those with a prior negative biopsy, BiRCH models can be used to select patients for mpMRI., Patient Summary: In this multicenter study, we developed and prospectively validated a calculator that can be used to predict prostate magnetic resonance imaging (MRI) results using patient age, prostate-specific antigen, and prostate volume as input. This tool can aid health care professionals and patients to make an informed decision regarding whether to get an MRI., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To investigate the effect of ambient music on anxiety and pain in men undergoing prostate biopsies., Materials and Methods: Between September 2015 and June 2016, men undergoing office transrectal prostate biopsy at our institution were randomly assigned to music (n = 85) or control (n = 97) groups. We examined clinical characteristics, pathologic variables, and baseline anxiety using the Trait Instrument of State-Trait Anxiety Inventory. Primary outcomes included anxiety assessed by State Instrument of STAI (STAI-S) and pain using a visual analog scale., Results: There were no significant differences in baseline characteristics between the music and control groups, including median age, prostate-specific antigen, use of magnetic resonance imaging-guided biopsies, or Trait Instrument of State-Trait Anxiety Inventory. The majority (93%) of patients indicated they desired music in their prebiopsy survey. There were no significant differences in STAI-S (33.7 ± 8.9 vs 34.4 ± 9.9, P = .6), pain score (2.3 ± 2.1 vs 2.0 ± 2.1, P = .3), or vital signs between the music and control groups, respectively. There were also no differences in STAI-S, visual analog scale, or vital signs between groups when stratified by age, prostate-specific antigen, or number of previous biopsies. Men who received music were more likely to request music for future prostate biopsy, compared to men who did not (93% vs 83%, P = .07, respectively)., Conclusion: This randomized study showed no difference in anxiety or pain scores for patients who had ambient music during transrectal prostate biopsy. Future studies are needed to discern the influence of details including method of music delivery, music type, and utilization of adjunct relaxation tools., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: To report the incidence and characteristics of cancer following a diagnosis of atypical small acinar proliferation (ASAP) and comment on current clinical practice recommendations., Materials and Methods: We reviewed patients that underwent prostate biopsy between 2008 and 2013 at a single institution. Men with ASAP without previous cancer were included. Clinicopathologic features including prostate-specific antigen (PSA), presence of ASAP or cancer, tumor volume, number of involved cores, and Gleason score were analyzed in men that received a repeat prostate biopsy., Results: Of 1450 men, ASAP was found in 75 (5%) patients. Repeat biopsy was performed in 49 (65%) patients. Fifteen (31%) were diagnosed with cancer, 10 (20%) with ASAP, and 24 (49%) were benign. PSA, age, and number of cores with ASAP were not associated with cancer. Gleason 6 disease was diagnosed in 12 (80%) patients. Gleason ≥ 7 cancer was found in 3 patients, or 6% of all patients with a repeat biopsy. The average linear amount of tumor was 3.2 mm, and the average tumor volume was 14.2%., Conclusion: In a contemporary prostate biopsy series, the incidence of ASAP was 5%. Among men with ASAP, incidence of cancer at repeat biopsy was 31%, with the overwhelming majority being low grade and low volume. Patients with ASAP may not require repeat biopsy within 6 months in the appropriate clinical context.

Context: Focal therapy of prostate cancer has been proposed as an alternative to whole-gland treatments., Objective: To summarize the evidence regarding sources of energy employed in focal therapy., Evidence Acquisition: Embase and Medline (PubMed) were searched from 1996 to October 31, 2015 following the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Ongoing trials were selected from electronic registries. The stage of assessment of each source of energy was determined using the Idea, Development, Exploration, Assessment, Long-term study recommendations., Evidence Synthesis: Thirty-seven articles reporting on 3230 patients undergoing focal therapy were selected. Thirteen reported on high-intensity focused ultrasound, 11 on cryotherapy, three on photodynamic therapy, four on laser interstitial thermotherapy, two on brachytherapy, three on irreversible electroporation, and one on radiofrequency. High-intensity focused ultrasound, cryotherapy, photodynamic therapy, and brachytherapy have been assessed in up to Stage 2b studies. Laser interstitial thermotherapy and irreversible electroporation have been evaluated in up to Stage 2a studies. Radiofrequency has been evaluated in one Stage 1 study. Median follow-up varied between 4 mo and 61 mo, and the median rate of serious adverse events ranged between 0% and 10.6%. Pad-free leak-free continence and potency were obtained in 83.3-100% and 81.5-100%, respectively. In series with intention to treat, the median rate of significant and insignificant disease at control biopsy varied between 0% and 13.4% and 5.1% and 45.9%, respectively. The main limitations were the length of follow-up, the absence of a comparator arm, and study heterogeneity., Conclusions: Focal therapy has been evaluated using seven sources of energy in single-arm retrospective and prospective development studies up to Stage 2b. Focal therapy seems to have a minor impact on quality of life and genito-urinary function. Oncological effectiveness is yet to be defined against standard of care., Patient Summary: Seven sources of energy have been employed to selectively ablate discrete areas of prostate cancer. There is high evidence that focal therapy is safe and has low detrimental impact on continence and potency. The oncological outcome has yet to be evaluated against standard of care., (Copyright © 2016 European Association of Urology. All rights reserved.)

Purpose: After an initial negative biopsy there is an ongoing need for strategies to improve patient selection for repeat biopsy as well as the diagnostic yield from repeat biopsies., Materials and Methods: As a collaborative initiative of the AUA (American Urological Association) and SAR (Society of Abdominal Radiology) Prostate Cancer Disease Focused Panel, an expert panel of urologists and radiologists conducted a literature review and formed consensus statements regarding the role of prostate magnetic resonance imaging and magnetic resonance imaging targeted biopsy in patients with a negative biopsy, which are summarized in this review., Results: The panel recognizes that many options exist for men with a previously negative biopsy. If a biopsy is recommended, prostate magnetic resonance imaging and subsequent magnetic resonance imaging targeted cores appear to facilitate the detection of clinically significant disease over standardized repeat biopsy. Thus, when high quality prostate magnetic resonance imaging is available, it should be strongly considered for any patient with a prior negative biopsy who has persistent clinical suspicion for prostate cancer and who is under evaluation for a possible repeat biopsy. The decision of whether to perform magnetic resonance imaging in this setting must also take into account the results of any other biomarkers and the cost of the examination, as well as the availability of high quality prostate magnetic resonance imaging interpretation. If magnetic resonance imaging is done, it should be performed, interpreted and reported in accordance with PI-RADS version 2 (v2) guidelines. Experience of the reporting radiologist and biopsy operator are required to achieve optimal results and practices integrating prostate magnetic resonance imaging into patient care are advised to implement quality assurance programs to monitor targeted biopsy results., Conclusions: Patients receiving a PI-RADS assessment category of 3 to 5 warrant repeat biopsy with image guided targeting. While transrectal ultrasound guided magnetic resonance imaging fusion or in-bore magnetic resonance imaging targeting may be valuable for more reliable targeting, especially for lesions that are small or in difficult locations, in the absence of such targeting technologies cognitive (visual) targeting remains a reasonable approach in skilled hands. At least 2 targeted cores should be obtained from each magnetic resonance imaging defined target. Given the number of studies showing a proportion of missed clinically significant cancers by magnetic resonance imaging targeted cores, a case specific decision must be made whether to also perform concurrent systematic sampling. However, performing solely targeted biopsy should only be considered once quality assurance efforts have validated the performance of prostate magnetic resonance imaging interpretations with results consistent with the published literature. In patients with negative or low suspicion magnetic resonance imaging (PI-RADS assessment category of 1 or 2, respectively), other ancillary markers (ie PSA, PSAD, PSAV, PCA3, PHI, 4K) may be of value in identifying patients warranting repeat systematic biopsy, although further data are needed on this topic. If a repeat biopsy is deferred on the basis of magnetic resonance imaging findings, then continued clinical and laboratory followup is advised and consideration should be given to incorporating repeat magnetic resonance imaging in this diagnostic surveillance regimen., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To compare pathological characteristics, treatment patterns, and survival in patients with ductal adenocarcinoma (DC) compared to those with acinar adenocarcinoma (AC)., Materials and Methods: Using the National Cancer Database, we identified patients diagnosed with clinically localized (cN0, cM0) pure DC (n = 1328) and AC (n = 751,635) between 1998 and 2011. High-risk AC was defined as Gleason 8-10. Demographic, treatment, pathological, and survival characteristics of patients were compared., Results: Compared to patients with Gleason 8-10 AC, those with DC presented with lower mean prostate-specific antigen (10.3 vs 16.2 ng/mL, P <.001), had similar rates (11.7% vs 11.5%, P = .8) of clinical extra-capsular extension (stage ≥ cT3), and were more likely to undergo prostatectomy (54% vs 36%, P <.001). Compared to patients with Gleason 8-10 AC undergoing prostatectomy, those with DC had more favorable pathology: stage ≥ T3 (39% vs 52%, P <.001), fewer positive lymph nodes (4% vs 11%, P <.001), and fewer positive margins (25% vs 33%, P <.001). On Kaplan-Meier analysis, patients with DC had similar 5-year survival (75.0%, 95% confidence interval [CI] [71.7-78.9]) compared to those with Gleason 8-10 AC (77.1%, 95% CI [76.6%-77.6%], P = .2). On Cox multivariable analysis, patients with Gleason 8-10 AC had a similar risk of death compared to those with DC (hazards ratio = 0.92, 95% CI [0.69-1.23], P = 6)., Conclusion: In this large contemporary population-based series, patients with DC of the prostate presented with lower prostate-specific antigen, had more favorable pathological features, and similar overall survival compared to men with Gleason 8-10 AC., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: To summarize the results of a 4-year period in which endorectal magnetic resonance imaging (MRI) was considered for all men referred for salvage radiation therapy (RT) at a single academic center; to describe the incidence and location of locally recurrent disease in a contemporary cohort of men with biochemical failure after radical prostatectomy (RP), and to identify prognostic variables associated with MRI findings in order to define which patients may have the highest yield of the study., Methods and Materials: Between 2007 and 2011, 88 men without clinically palpable disease underwent eMRI for detectable prostate-specific antigen (PSA) after RP. The median interval between RP and eMRI was 32 months (interquartile range, 14-57 months), and the median PSA level was 0.30 ng/mL (interquartile range, 0.19-0.72 ng/mL). Magnetic resonance imaging scans consisting of T2-weighted, diffusion-weighted, and dynamic contrast-enhanced imaging were evaluated for features consistent with local recurrence. The prostate bed was scored from 0-4, whereby 0 was definitely normal, 1 probably normal, 2 indeterminate, 3 probably abnormal, and 4 definitely abnormal. Local recurrence was defined as having a score of 3-4., Results: Local recurrence was identified in 21 men (24%). Abnormalities were best appreciated on T2-weighted axial images (90%) as focal hypointense lesions. Recurrence locations were perianastomotic (67%) or retrovesical (33%). The only risk factor associated with local recurrence was PSA; recurrence was seen in 37% of men with PSA >0.3 ng/mL vs 13% if PSA ≤0.3 ng/mL (P<.01). The median volume of recurrence was 0.26 cm(3) and was directly associated with PSA (r=0.5, P=.02). The correlation between MRI-based tumor volume and PSA was even stronger in men with positive margins (r=0.8, P<.01)., Conclusions: Endorectal MRI can define areas of local recurrence after RP in a minority of men without clinical evidence of disease, with yield related to PSA. Further study is necessary to determine whether eMRI can improve patient selection and success of salvage RT., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: To evaluate feasibility of high-resolution, high-field ex vivo prostate magnetic resonance imaging (MRI) as an aid to guide pathologists' examination and develop in vivo MRI methods., Materials and Methods: Unfixed excised prostatectomy specimens (n = 9) were obtained and imaged immediately after radical prostatectomy under an Institutional Review Board-approved protocol. High-resolution T2-weighted (T2W) MRI of specimens were acquired with a Bruker 9.4 T scanner to correlate with whole-mount histology. Additionally, T2 and apparent diffusion coefficient (ADC) maps were generated., Results: By visual inspection of the nine prostate specimens imaged, high-resolution T2W MRI showed improved anatomical detail compared to published low-resolution images acquired at 4 T as published by other investigators. Benign prostatic hyperplasia, adenocarcinomas, curvilinear duct architecture distortion due to adenocarcinomas, and normal radial duct distribution were readily identified. T2 was ≈10 msec longer (P < 0.03) and the ADC was ≈1.4 times larger (P < 0.002) in the normal peripheral zone compared to the peripheral zone with prostate cancer., Conclusion: Differences in T2 and ADC between benign and malignant tissue are consistent with in vivo data. High-resolution, high-field MRI has the potential to improve the detection and identification of prostate structures. The protocols and techniques developed in this study could augment routine pathological analysis of surgical specimens and guide treatment of prostate cancer patients., (Copyright © 2011 Wiley-Liss, Inc.)

Background and Purpose: Patients with Gleason (GL) 6 prostate cancer in one or two biopsy cores can be upgraded and/or upstaged at the time of surgery, which may adversely impact long-term outcome. A novel model for prediction of adverse pathologic outcomes was developed using preoperative characteristics., Patients and Methods: Between 2003 and 2007, 1159 patients underwent robot-assisted radical prostatectomy (RARP) at our institution. GL 6 prostate cancer in one or two biopsy cores was identified in 416 (36%) patients. Logistic regression analyses were used to assess the rate of GL ≥7 and/or extraprostatic extension at RARP. Covariates consisted of age, body mass index (BMI), number of positive cores, greatest percent of cancer in a core (GPC), clinical stage, and preoperative prostate-specific antigen (PSA) level. After backward variable selection, the developed model was internally validated using the area under the curve and subjected to methods of calibration., Results: Respectively, 278 (67%) and 138 (33%) patients had one or two positive biopsy cores. At RARP, 90 (22%) patients were upgraded to GL ≥7 and 37 (9%) had extraprostatic extension. The novel model relied on age, BMI, preoperative PSA level, and GPC for prediction of adverse pathologic outcomes and was 69% accurate. Calibration plot revealed a virtually perfect relationship between predicted and observed probabilities., Conclusions: In patients with GL 6 prostate cancer in one or two biopsy cores, 25% have more ominous pathology at RARP. The model provides an individual assessment of adverse outcomes at surgery. Consequently, it may be considered when counseling patients regarding their management options.

This article discusses the use of percentage of free prostate-specific antigen (%fPSA) as a biomarker for prostate cancer (PCa) risk. While %fPSA has been widely used in the diagnosis and management of PCa, the article argues that reporting risk estimates for unselected PCa based on %fPSA can be misleading and potentially harmful. The authors suggest that the focus should be on minimizing the diagnosis of low-risk PCa while maintaining sensitivity for higher-grade cancers. They recommend removing risk estimates for unselected PCa from laboratory reports and encourage other institutions to consider doing the same. [Extracted from the article]

Purpose Magnetic resonance imaging guided focal laser ablation is an investigational strategy for the treatment of prostate cancer. Materials and Methods This phase II evaluation of focal laser ablation included men with stage T1c-T2a, prostate specific antigen less than 15 ng/ml or prostate specific antigen density less than 0.15 ng/ml 3 , Gleason 7 or less in 25% or less of biopsies and magnetic resonance imaging with 1 or 2 lesions concordant with biopsy detected cancer. At 3 months all patients underwent magnetic resonance imaging with biopsy of ablation zone(s). At 12 months all underwent magnetic resonance imaging and systematic biopsy. I-PSS (International Prostate Symptom Score) and SHIM (Sexual Health Inventory for Men) scores were collected before focal laser ablation, and at 1, 3 and 12 months. The primary end point was no cancer on the 3-month ablation zone biopsy. Secondary end points were safety, 12-month biopsy, and urinary and sexual function. Results In the 27 men median age was 62 years and mean prostate specific antigen was 4.4 ng/ml. Biopsy Gleason score was 6 in 23 patients (85%) and Gleason 7 in 4 (15%). Seven men (26%) had low volume Gleason 6 disease outside the intended ablation zone(s). At 3 months 26 patients (96%) had no evidence of cancer on magnetic resonance imaging guided biopsy of the ablation zone. No significant I-PSS changes were observed (each p >0.05). SHIM was lower at 1 month (p = 0.03), marginally lower at 3 months (p = 0.05) and without a significant difference at 12 months (p = 0.38). At 12-month biopsy cancer was identified in 10 patients (37%), including in the ablation zone(s) in 3 (11%) and outside the ablation zone(s) in 8 (30%) with cancer in and outside the ablation zone in 1. Conclusions In select men with localized prostate cancer and visible magnetic resonance imaging lesions focal laser ablation has an acceptable morbidity profile and is associated with encouraging short-term oncologic outcomes. Significantly longer followup is mandatory to fully assess this novel treatment. [ABSTRACT FROM AUTHOR]

Purpose To our knowledge factors affecting the adoption of noncurative initial management in the United States for low risk prostate cancer on a population based level are unknown. We measured temporal trends in the proportion of patients with low and intermediate risk prostate cancer who elected noncurative initial treatment in the United States and analyzed the association of factors affecting management choice. Materials and Methods We identified 465,591 and 237,257 men diagnosed with low or intermediate risk prostate cancer using NCDB and SEER (2004 to 2010), respectively. We measured the proportion of men who elected noncurative initial treatment and used multivariate logistic regression analysis to evaluate factors affecting the treatment choice. Results During the study period noncurative initial management increased in patients at low risk from 21% to 32% in SEER and from 13% to 20% in NCDB (each p <0.001). This increase was not reflected in our overall study population (SEER 20% to 22% and NCDB 11% to 13%) since the proportion of patients with Gleason score 6 or less decreased with time (61% to 49% and 61% to 45%, respectively). From 2004 to 2010 older age, lower prostate specific antigen, earlier clinical stage, increased comorbidity index and not being married were associated with a higher likelihood of noncurative initial management (each p <0.05). Conclusions Two independently managed, population based data sets confirmed a temporal increase in noncurative initial management in patients with low risk PCa that did not translate into greater use overall in those at low and intermediate risk combined. These contrasting results are likely due to grade migration resulting in fewer men being classified as with low risk PCa based on Gleason score. [ABSTRACT FROM AUTHOR]

Purpose: Hazard is defined as an event rate at a certain time that is conditional on survival until that time. For most patients with localized malignancies the mortality hazard decreases with time after an initial period of high failure risk. We assessed prostate cancer specific mortality hazard changes with time in men treated with radical prostatectomy. Materials and Methods: The cohort included 127,236 men from the SEER (Surveillance, Epidemiology and End Results) database who were treated with RP between 1988 and 2003. Pathological stage was organ confined in 38,684 men (30%), nonorgan confined in 41,806 (33%) and unstaged in 46,746 (37%). Gleason score 7 or less was present in 100,816 men (79%) and Gleason score 8 or greater in 26,420 (21%). Patients were stratified into groups, including group 1—71,106 (59%) with Gleason score 7 or less, organ confined, group 2—23,063 (19%) with Gleason score 7 or less, nonorgan confined, group 3—13,660 (12%) with Gleason score 8 or greater, organ confined and group 4—12,158 (10%) with Gleason score 8 or greater, nonorgan confined tumors. Median followup was 7.2 years (range 0 to 19). Hazard was estimated from a Cox regression model including patient age, race, stage and grade. Results: The overall annual prostate cancer specific mortality hazard rate was 0.4%, 0.7% and 1% 5, 10 and 15 years after radical prostatectomy, respectively. Between 5 and 15 years after radical prostatectomy the hazard increased annually from 0.2% to 0.5% in group 1, from 0.5% to 1.2% in group 2, from 0.7% to 1.6% in group 3 and from 1.5% to 3.7% in group 4. Conclusions: In contrast to other prevalent cancers, the hazard of prostate cancer specific mortality shows a modest, constant increase for at least 15 years after radical prostatectomy. [Copyright &y& Elsevier]

Purpose: Long-term prostate cancer specific mortality after radical prostatectomy is poorly defined in the era of widespread screening. An understanding of the treated natural history of screen detected cancers and the pathological risk factors for prostate cancer specific mortality are needed for treatment decision making. Materials and Methods: Using Fine and Gray competing risk regression analysis we modeled clinical and pathological data, and followup information on 11,521 patients treated with radical prostatectomy at a total of 4 academic centers from 1987 to 2005 to predict prostate cancer specific mortality. The model was validated on 12,389 patients treated at a separate institution during the same period. Median followup in the modeling and validation cohorts was 56 and 96 months, respectively. Results: The overall 15-year prostate cancer specific mortality rate was 7%. Primary and secondary Gleason grade 4–5 (each p <0.001), seminal vesicle invasion (p <0.001) and surgery year (p = 0.002) were significant predictors of prostate cancer specific mortality. A nomogram predicting 15-year prostate cancer specific mortality based on standard pathological parameters was accurate and discriminating with an externally validated concordance index of 0.92. When stratified by patient age at diagnosis, the 15-year prostate cancer specific mortality rate for pathological Gleason score 6 or less, 3 + 4, 4 + 3 and 8–10 was 0.2% to 1.2%, 4.2% to 6.5%, 6.6% to 11% and 26% to 37%, respectively. The 15-year prostate cancer specific mortality risk was 0.8% to 1.5%, 2.9% to 10%, 15% to 27% and 22% to 30% for organ confined cancer, extraprostatic extension, seminal vesicle invasion and lymph node metastasis, respectively. Only 3 of 9,557 patients with organ confined, pathological Gleason score 6 or less cancer died of prostate cancer. Conclusions: Poorly differentiated cancer and seminal vesicle invasion are the prime determinants of prostate cancer specific mortality after radical prostatectomy. The prostate cancer specific mortality risk can be predicted with remarkable accuracy after the pathological features of prostate cancer are known. [Copyright &y& Elsevier]

Purpose: Active surveillance with selective delayed intervention is a treatment regimen used in patients with low risk prostate cancer. Decision making is based on pretreatment prostate specific antigen, clinical stage and prostate biopsy results. We reviewed our experience with immediate repeat biopsy in patients eligible for active surveillance with selective delayed intervention. Materials and Methods: A retrospective review was done of the records of consecutive patients who underwent repeat biopsy within 3 months of a first positive biopsy from March 2002 to June 2007. Patients were considered eligible if they had prostate specific antigen less than 10 ng/ml, clinical stage T2a or less, Gleason pattern 3 or less, 3 or fewer positive cores and no single core with 50% or greater cancer involvement. Results: A total of 104 patients met eligibility criteria. Of the 104 repeat biopsies performed 27 (26%) were negative, 59 (57%) had a Gleason score of 6 or less and 17 (16%) had a Gleason score of 7. One patient had a Gleason score of 9, while 10 of 104 (10%) had greater than 3 cores involved on repeat biopsy and 12 (12%) had 50% or greater involvement of at least 1 core. Of 104 cases (27%) 28 were upgraded and/or up staged. Treated cases that were upgraded and/or up staged were more likely to show higher pathological stage and grade at radical prostatectomy than those that were not (p = 0.003 and p = 0.001, respectively). Conclusions: Immediate repeat biopsy in cases of active surveillance with selective delayed intervention resulted in 27% being upgraded or up staged and those were more likely to show higher grade and stage disease at radical prostatectomy. We recommend repeat biopsy because it improved our discrimination of who are the best candidates for active surveillance with selective delayed intervention. [Copyright &y& Elsevier]

Purpose: Standardized criteria are lacking to define high risk, clinically localized prostate cancer before definitive treatment. Reliance on simple risk stratification schemes to define high risk cancers has led many physicians and patients toward therapeutic nihilism, inappropriately selecting androgen deprivation instead of definitive local therapy. Of patients undergoing radical prostatectomy we identified those at high risk based on 8 previously described definitions. We examined pathological characteristics and prostate specific antigen outcomes. Materials and Methods: The study population included 4,708 men treated with radical prostatectomy alone between 1985 and 2004. Estimates of prostate specific antigen relapse for patients at high risk were generated with the Kaplan-Meier method. Cox proportional hazards regression was used to estimate the HR for recurrence in high risk vs nonhigh risk cohorts. Results: Depending on the definition used patients at high risk composed 3% to 38% of the study population. The proportion of patients with extracapsular extension, seminal vesicle invasion and lymph node metastasis among men with high risk cancer was 35% to 71%, 10% to 33% and 7% to 23%, respectively. Of the high risk tumors 22% to 63% proved to be confined to the prostate pathologically. While patients at high risk had a 1.8 to 4.8-fold increased hazard of prostate specific antigen relapse, their 5-year relapse-free probability after radical prostatectomy alone was 49% (95% CI 39 to 58) to 80% (95% CI 77 to 83). Of patients at high risk who had relapse 25% across all definitions experienced relapse more than 2 years after surgery and in 26% to 39% prostate specific antigen doubling time at recurrence was 10 months or greater. Conclusions: Patients diagnosed with high risk cancer by currently available definitions do not have a uniformly poor prognosis after radical prostatectomy. Many cancers classified clinically as high risk are actually confined to the prostate pathologically. The risk of extraprostatic disease and prostate specific antigen relapse varies greatly depending on the definition used. [Copyright &y& Elsevier]

Abstract: Objective: Screening using a standardized protocol may improve outcomes of patients undergoing treatment for prostate cancer. We compared the 7- year progression-free survival rates after radical retropubic prostatectomy in patients whose prostate cancer was detected through a formal screening program with those of patients referred for treatment by other physicians who did not use a standardized screening/referral protocol. Methods: A single surgeon (W.J.C.) performed radical retropubic prostatectomy in 3,177 consecutive patients between 1989 and 2003. Of these patients, 464 had cancer detected in a screening study, and 2,713 were referred from outside institutions. We compared the screened and referred cohorts for age at surgery, clinical stage, pathologic stage, Gleason sum, preoperative prostate-specific antigen (PSA) levels, and adjuvant radiation therapy. Kaplan-Meier product limit estimates were used to calculate 7-year progression-free probabilities, and Cox proportional hazards models were used to determine the clinical and pathologic parameters associated with cancer progression in each group. Results: The overall 7-year progression-free survival rates were 83% for the screened patients compared with 77% for the referred patients (P = 0.002). Preoperative PSA, Gleason sum, clinical stage, pathologic stage, and adjuvant radiotherapy were all significantly associated with cancer progression. There was a significantly higher proportion of referred patients with a preoperative PSA ≥10, Gleason sum ≥7, and nonorgan-confined disease. Conclusions: Patients with screened-detected prostate cancer have more favorable clinical and pathologic features, and 7-year progression-free survival rates than referred patients. On multivariate analysis, including other clinical variables, screening status was a significant independent predictor of biochemical outcome. [Copyright &y& Elsevier]

Purpose: Prostate specific antigen velocity 2.0 ng/ml per year or greater in the year before prostate cancer diagnosis is associated with cancer specific survival following radical prostatectomy and radiation therapy. We evaluated the relationship between prediagnosis prostate specific antigen velocity and cancer progression following primary radiation therapy. Materials and Methods: We analyzed the records of 24,893 men from a community based prostate cancer screening study and identified 237 with clinically localized prostate cancer who elected primary radiation therapy. Our final cohort consisted of 130 men, including 83 treated with external beam radiation and 47 treated with brachytherapy. Patient specific variables at diagnosis were analyzed for their value in predicting biochemical progression using American Society for Therapeutic and Radiation Oncology criteria. Results: Mean followup ± SD was 64 ± 35 months. Prostate specific antigen at diagnosis, family history of prostate cancer and prediagnosis prostate specific antigen velocity 2.0 ng/ml per year or greater were associated with cancer progression following brachytherapy or external beam radiation. Of men with prostate specific antigen velocity 2.0 ng/ml per year or greater 38% had cancer progression compared to 12% with prostate specific antigen velocity less than 2.0 ng/ml per year (OR 4.3, p = 0.003). The 6-year progression-free survival estimate was 57% in men with prostate specific antigen velocity 2.0 ng/ml per year or greater and 82% in men with prostate specific antigen velocity less than 2.0 ng/ml per year (p <0.001). On multivariate analysis absolute prostate specific antigen at diagnosis and prostate specific antigen velocity 2.0 ng/ml per year or greater were independently associated with cancer progression in men treated with external beam radiation therapy or brachytherapy. Conclusions: Men with a prediagnosis prostate specific antigen velocity of 2.0 ng/ml per year or greater are at increased risk for cancer progression following brachytherapy or external beam radiation compared to men with a prostate specific antigen velocity of less than 2.0 ng/ml per year. [Copyright &y& Elsevier]

The article focuses on a 55-year-old male patient with urinary retention, gross hematuria, concern for bladder mass and an increased prostate specific antigen (PSA), who was referred to the University of Chicago. The patient has a history of gradually worsening lower urinary tract symptoms, including incomplete emptying, frequency and nocturia. He experienced gross hematuria and underwent cystoscopy procedure with clot evacuation.

Context The incidence of low-risk prostate cancer (PCa) has increased as a consequence of prostate-specific antigen testing. Objective In this collaborative review article, we examine recent literature regarding low-risk PCa and the available prognostic and therapeutic options. Evidence acquisition We performed a literature review of the Medline, Embase, and Web of Science databases. The search strategy included the terms: prostate cancer, low risk, active surveillance, focal therapy, radical prostatectomy, watchful waiting, biomarker, magnetic resonance imaging, alone or in combination. Evidence synthesis Prospective randomized trials have failed to show an impact of radical treatments on cancer-specific survival in low-risk PCa patients. Several series have reported the risk of adverse pathologic outcomes at radical prostatectomy. However, it is not clear if these patients are at higher risk of death from PCa. Long-term follow-up indicates the feasibility of active surveillance in low-risk PCa patients, although approximately 30% of men starting active surveillance undergo treatment within 5 yr. Considering focal therapies, robust data investigating its impact on long-term survival outcomes are still required and therefore should be considered experimental. Magnetic resonance imaging and tissue biomarkers may help to predict clinically significant PCa in men initially diagnosed with low-risk disease. Conclusions The incidence of low-risk PCa has increased in recent years. Only a small proportion of men with low-risk PCa progress to clinical symptoms, metastases, or death and prospective trials have not shown a benefit for immediate radical treatments. Tissue biomarkers, magnetic resonance imaging, and ongoing surveillance may help to identify those men with low-risk PCa who harbor more clinically significant disease. Patient summary Low-risk prostate cancer is very common. Active surveillance has excellent long-term results, while randomized trials have failed to show a beneficial impact of immediate radical treatments on survival. Biomarkers and magnetic resonance imaging may help to identify which men may benefit from early treatment. [ABSTRACT FROM AUTHOR]

Objective: To evaluate how blood levels of prostate-specific antigen (PSA) relate to prostate volume of benign tissue, Gleason pattern 3 (GP3) and Gleason pattern 4 (GP4) cancer.Methods: The cohort included 2209 consecutive men undergoing radical prostatectomy at 2 academic institutions with pT2N0, Grade Group 1-4 prostate cancer and an undetectable postoperative PSA. Volume of benign, GP3, and GP4 were estimated. The primary analysis evaluated the association between PSA and volume of each type of tissue using multivariable linear regression. R2, a measure of explained variation, was calculated using a multivariable model.Results: Estimated contribution to PSA was 0.04/0.06 ng/mL/cc for benign, 0.08/0.14 ng/mL/cc for GP3, and 0.62/0.80 ng/ml/cc for GP4 for the 2 independent cohorts, respectively. GP4 was associated with 6 to 8-fold more PSA per cc compared to GP3 and 15-fold higher compared to benign tissue. We did not observe a difference between PSA per cc for GP3 vs. benign tissue (P = 0.2). R2 decreased only slightly when removing age (0.006/0.018), volume of benign tissue (0.051/0.054) or GP3 (0.014/0.023) from the model. When GP4 was removed, R2 decreased 0.051/0.310. PSA density (PSA divided by prostate volume) was associated with volume of GP4 but not GP3, after adjustment for benign volume.Conclusion: Gleason pattern 4 cancer contributes considerably more to PSA and PSA density per unit volume compared to GP3 and benign tissue. Contributions from GP3 and benign are similar. Further research should examine the utility of determining clinical management recommendations by absolute volume of GP4 rather than the ratio of GP3 to GP4. [ABSTRACT FROM AUTHOR]